Quick Comparison
| 5-HTP | Magnesium Glycinate | |
|---|---|---|
| Half-Life | 2-5 hours | 12-17 hours |
| Typical Dosage | Standard: 50-200 mg daily. For mood: 50-100 mg 2-3 times daily. For sleep: 100-300 mg 30-60 minutes before bed. Start low — some people are very sensitive. Take with food to reduce nausea. | Standard: 200-400 mg elemental magnesium daily (note: magnesium glycinate is ~14% elemental magnesium by weight, so 2000 mg magnesium glycinate provides ~280 mg elemental). Take in the evening for sleep benefits. Can be split into 2 doses. |
| Administration | Oral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits. | Oral (capsules, powder, tablets). Well-tolerated. Take with or without food. |
| Research Papers | 10 papers | 8 papers |
| Categories |
Mechanism of Action
5-HTP
5-HTP readily crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1/SLC7A5), unlike serotonin itself which cannot. Once in the brain, aromatic L-amino acid decarboxylase (AADC, also called DOPA decarboxylase) converts 5-HTP to serotonin (5-hydroxytryptamine) using pyridoxal-5-phosphate (active vitamin B6) as a cofactor. This completely bypasses tryptophan hydroxylase (TPH2), the rate-limiting enzyme in the normal serotonin synthesis pathway from dietary L-tryptophan. The result is a reliable, dose-dependent increase in serotonin across multiple brain regions including the dorsal raphe nucleus, hippocampus, and prefrontal cortex. Elevated serotonin activates 5-HT1A autoreceptors (calming), 5-HT2A/2C postsynaptic receptors (mood modulation), and 5-HT3 receptors (gut-brain signaling). In the pineal gland, serotonin is converted by arylalkylamine N-acetyltransferase (AANAT) to N-acetylserotonin, then by hydroxyindole O-methyltransferase (HIOMT) to melatonin — explaining the sleep-promoting effects.
Magnesium Glycinate
Magnesium is required for over 300 enzymatic reactions including neurotransmitter synthesis (tyrosine hydroxylase, tryptophan hydroxylase), energy production (ATPases, kinases, glycolytic enzymes), and DNA repair (PARP, DNA polymerases). In the brain, magnesium blocks NMDA receptors at the voltage-dependent Mg2+ binding site within the channel pore (GluN1/GluN2 subunits), preventing excessive calcium influx and excitotoxicity — Mg2+ is displaced only upon depolarization and glycine/glutamate binding. The glycine component activates inhibitory glycine receptors (GlyR alpha1/alpha2) in the brainstem and spinal cord, and serves as an obligatory co-agonist at the GluN1 glycine site of NMDA receptors. Glycine also modulates NMDA receptor function. Together, magnesium and glycine produce calming effects through complementary inhibitory mechanisms: reduced glutamatergic excitability and enhanced inhibitory neurotransmission.
Risks & Safety
5-HTP
Common
Nausea, diarrhea, stomach cramps.
Serious
Serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or tramadol — DO NOT combine without medical supervision.
Rare
Eosinophilia-myalgia syndrome (historical concern from contaminated L-tryptophan, not confirmed with modern 5-HTP).
Magnesium Glycinate
Common
Mild drowsiness (often desired), loose stools at high doses (less than with other forms).
Serious
Avoid high doses with kidney impairment.
Rare
Diarrhea, nausea.
Full Profiles
5-HTP →
5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.
Magnesium Glycinate →
A highly bioavailable form of magnesium chelated with glycine. The glycine component adds its own calming effects (inhibitory neurotransmitter), making this form particularly effective for anxiety, sleep, and stress. Better tolerated than magnesium citrate or oxide with fewer GI side effects. Magnesium deficiency affects an estimated 50-80% of adults and directly impairs cognitive function.